Maternal myo-inositol, glucose, and zinc status is associated with the risk of offspring with spina bifida

Objective

The purpose of this study was to investigate the maternal and children's myo-inositol, glucose, and zinc status in association with spina bifida risk.

Study design

Sixty-three mothers and 70 children with spina bifida and 102 control mothers and 85 control children were investigated. The maternal and child serum myo-inositol, serum glucose, and red blood cell zinc concentrations were measured when the child was between 1 and 3 years old. These data were compared between cases and control subjects. The association with spina bifida was expressed by the ratio of geometric means and by odds ratios and 95% CI for a cutoff value at the extreme 10th percentile of the control group.

Results

The geometric mean of the maternal myo-inositol concentration tended to be 5% (95% CI, −1% to 11%) lower in cases. Interestingly, the odds ratio for the extreme low maternal myo-inositol concentration was 2.6 (95% CI, 1.1-6.0). The glucose and zinc concentrations were significantly higher at 7% (95% CI, 4%-10%) and significantly lower at 5% (95% CI, 0%-9%), in case mothers compared with control mothers. The odds ratios (95% CI) for maternal high glucose and low zinc concentrations were 4.6 (2.0-10.5) and 2.9 (1.2-7.0), respectively. The geometric mean of the myo-inositol concentration tended to be 7% (95% CI, 0%-14%) lower in children with spina bifida; the glucose and zinc concentrations were comparable.

Conclusion

Maternal myo-inositol, glucose, and zinc status are associated with the risk of spina bifida in offspring. Furthermore, the myo-inositol status of the child seems to contribute to this risk as well.     

Sclerosing cholangitis revealing histiocytosis X

The case of a 3 year-old boy who presented isolated cholestasis as the initial symptom of histiocytosis X is described. Other symptoms occurred later on. Despite treatment (corticosteroid and Vinblastin), the disease continued to progress and the child died at the age of 4 1/2 years with HIV infection (contaminated blood product) and tuberculosis.     

Wilson's disease with liver copper in normal concentration

The cases of 2 children with Wilson's disease revealed by persistent hypertransaminasemia are reported. Blood ceruloplasmin concentration was low but the liver content of copper was lower than usually seen in presymptomatic forms of the disease. The apparently low liver copper concentration could be explained by an unusually important steatosis.     

The effects of thiol moiety of levamisole on both cellular and humoral immunity during the early response to a hapten-carrier complex.

Cell-mediated reactions to the carrier and antibody-mediated reactions to the hapten were studied in guinea-pigs treated with a single i.v. injection of the thiol moiety of levamisole (DTC), before or after immunization with a hapten-carrier complex. The results show that a heavy dose of DTC induced delayed hypersensitivity reactions to the carrier and decreased antibody synthesis to the hapten. On the other hand, with a small dose of DTC no delayed hypersensitivity could be induced, but antibody synthesis to the hapten was depressed or enhanced, depending upon whether the injection was done before or after immunization. The mechanisms whereby DTC modulated the immune response are discussed.     

Early effects of unilateral lesions of substantia nigra on immune reactivity.

It has recently been demonstrated that central dopaminergic pathways are asymmetrically involved in the modulation of the immune response. Mitogen-induced proliferation of T lymphocytes was shown to be enhanced 4-6 weeks after right lesion of the substantia nigra (SN) in mice, when compared to left lesioned and control animals. In order to study the involvement of post lesion neuronal reorganization in these results, the same immunological parameters were determined as early as 2 weeks after right or left lesion of the SN. We showed that the lymphoproliferation induced by alpha CD3 and concanavalin A was decreased in both lesioned groups, but phytohemagglutinin-induced mitogenesis was more impaired in the right than in the left lesioned animals. Hence, the time course effects of the right lesions of SN shifted from depression to enhancement of the T lymphocyte responsiveness. This shift appeared to occur around the two weeks period following the lesion. These immunomodulatory effects of unilateral SN lesioning, which depended on time and side of lesion, were similar to those observed after hemidecortication. Based on these findings, it is reasonable to suggest that asymmetry in brain immunomodulation involves functionally related dopaminergic and cortical networks.     

GPLA antigens are not expressed on guinea-pig epididymal spermatozoa

The expression of guinea-pig major histocompatibility antigens (class I and II) has been investigated on guinea-pig epididymal spermatozoa. Specific alloantisera (anti-B1, anti-B3, anti-Ia2,4 and anti-Ia1,3,7) were obtained by cross-immunization of strains 2, 13 and BIO-AD animals with relevant spleen cell membranes. These sera were tested on spermatozoa from the same three strains by a protein A rosetting assay and by an indirect immunofluorescence test. The results obtained showed non-strain specific reactions of all the alloantisera tested on epididymal spermatozoa of the three strains. These non-strain specific reactions were absorbed by spermatozoa of any strain but they were not absorbed by the splenic cells of the same animals. On the other hand, the alloantisera specific reactivity on peripheral blood cells was not diminished after incubation of the sera with spermatozoa. Furthermore anti-B1 and anti-B3 antibodies eluted from guinea-pig platelets did not react with any spermatozoa but reacted with the relevant peripheral blood cells. These results indicate that the studied guinea-pig sera contained two types of antibodies: anti-MHC antibodies able to react with relevant blood cells but not with spermatozoa and sperm specific antibodies (also observed in untreated and DNP-BGG immunized guinea-pig sera) reacting with all spermatozoa but not with blood cells. They are not compatible with the expression of MHC antigens at the surface of guinea-pig epididymal spermatozoa.     

Two high-voltage-activated,dihydropyridine-sensitive Ca2+ channel currents with distinct electrophysiological and pharmacological properties in cultured rat aortic myocytes

In smooth muscle cells, essentially two distinct types of voltage-gated Ca²⁺ channels have been shown, on the basis of their distinct electrophysiological and pharmacological properties, to coexist. Here we report that, in addition to a dihydropyridine (DHP)-sensitive, low-voltage-activated Ba²⁺ current (I _Ba,LVA), two types of high-voltage-activated Ba²⁺ currents with distinct waveforms were recorded in whole-cell clamped aortic myocytes; these were referred to as I _Ba,HVA1 and I _Ba,HVA2. They were investigated in cells where no I _Ba,LVA was detectable. I _Ba,HVA1 had a slow, monoexponential decay. In contrast, the decay of I _Ba,HVA2 was much faster and biexponential. In addition, I _Ba,HVA2 had more negative ranges of activation and steady-state inactivation than I _Ba,HVA1 and was more sensitive to the DHP antagonist nicardipine (concentrations for half maximum inhibition 0.2 M and 2 M, respectively). When using the physiological ion Ca²⁺ as the charge carrier, the decay of HVA1 currents was not altered, whereas both time constants of HVA2 current decay were accelerated fivefold. Moreover, permeability ratios (I _Ca/I _Ba) were also significantly different (0.2 and 0.6 for HVA1 and HVA2 respectively). I _Ba,HVA1 and I _Ba,HVA2 are consistent either with the existence and activation of two functionally distinct subtypes of the so-called DHP-sensitive L-type Ca²⁺ channel or with different gating behaviours of a single type of channel. Potentially, they may serve distinct biological functions and constitute distinct targets for neurotransmitters and drugs.     

The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast cells

The activity of granzyme B, a main effector molecule of cytotoxic T lymphocytes (CTL) and natural killer cells, is regulated by the human intracellular serpin proteinase inhibitor 9 (PI9). This inhibitor is particularly expressed by CTL and dendritic cells, in which it serves to protect these cells against endogenous and locally released granzyme B. Moreover, PI9 expression by neoplastic cells may constitute one of the mechanisms for tumors to escape immune surveillance. Here we show that PI9 is also expressed by human mast cells. In immunohistochemical studies using a PI9-specific monoclonal antibody, strong cytoplasmic staining for PI9 was found in normal mast cells in various tissues throughout the body. In addition, in 80% of all cases of cutaneous and systemic mastocytosis tested the majority of the mast cells expressed PI9. As an in vitro model for PI9 expression by mast cells, we studied expression by the human mast cell line HMC-1. Stimulation of HMC-1 with PMA and the calcium ionophore A23187 resulted in a marked increase of PI9 expression. Thus, PI9 is expressed by activated mast cells. We suggest that this expression serves to protect these cells against apoptosis induced by granzyme B released during initiation of the local inflammatory response.     

Dendritic cells transfected with the nef genes of HIV-1 primary isolates specifically activate cytotoxic T lymphocytes from seropositive subjects

The HIV-1 Nef protein down-modulates surface expression of MHC class I proteins. Primary infected T lymphocytes thus escape lysis by cytotoxic T lymphocytes (CTL). In contrast, during HIV-1 infection there are strong CTL responses to several HIV proteins, and there is mounting evidence that CTL are critical for controlling the virus. The present study was carried out to assess Nef protein-cell interaction as it occurs in naturally infected antigen-presenting cells. To evaluate the presentation of peptides derived from viral antigen to CTL, we transfected nef genes obtained from peripheral blood mononuclear cells of HIV-1-seropositive subjects into dendritic cells isolated from monocytes of healthy donors. We demonstrate that expression and subsequent processing of Nef by transfected dendritic cells did not alter the presentation of an immunodominant epitope of Nef to CTL of HIV ⁺ subjects. However, mutations in nef gene sequences from primary isolates may abolish this presentation by a mechanism that probably interferes with protein processing.